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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 022387/S-008
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`United Therapeutics Corp.
`Attention: Rex Mauthe, MBA
`Sr. Director, Regulatory Affairs
`55 TW Alexander Drive
`P.O. Box 14186
`Research Triangle Park, NC 27709
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`Dear Mr. Mauthe:
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`Please refer to your Supplemental New Drug Application (sNDA) dated October 3, 2012 and
`received October 4, 2012, submitted under section 505(b)(1) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Tyvaso (treprostinil) 0.6 mg/mL Inhalation Solution.
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`We acknowledge submission of your amendments dated October 11, and October 26, 2012.
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`This “Prior Approval” supplemental new drug application provides for labeling revised as
`follows (additions are marked as underlined text and deletions are marked as strikethrough text):
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`1. Under ADVERSE REACTIONS/Adverse Reactions Identified in Clinical Trials, the
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`following text was added:
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`The safety of Tyvaso was also studied in a long-term, open-label extension study
`in which 206 patients were dosed for a mean duration of 2.3 years, with a
`maximum exposure of 5.4 years. Eighty-nine (89%) percent of patients achieved
`the target dose of nine breaths, four times daily. Forty-two (42%) percent
`achieved a dose of 12 breaths four times daily. The adverse events during this
`chronic dosing study were qualitatively similar to those observed in the 12-week
`placebo controlled trial.
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`2. Under ADVERSE REACTIONS/Adverse Events Associated with Route of
`Administration, the number “8” was deleted and replaced with the word “fifteen” in the
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`first paragraph.
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`3. Under ADVERSE REACTIONS, a new section was added:
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`Reference ID: 3301325
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` NDA 022387/S-008
`Page 2
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`6.2
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` Adverse Reactions Identified in Post-Marketing Experience
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`The following adverse reaction has been identified during the
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`postapproval use of Tyvaso: Because this reaction is reported voluntarily from a
`population of uncertain size, it is not always possible to reliably estimate the
`frequency or establish a causal relationship to drug exposure:
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`Angioedema.
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`4. The name “treprostinil diethanolamine” was changed to “treprostinil diolamine”.
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`5. The revision date and version number were updated.
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`There are no other changes from the last approved package insert.
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`We have completed our review of this supplemental application, as amended, and it is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert), with the
`addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as
`well as annual reportable changes not included in the enclosed labeling.
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
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`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
`Also within 14 days, amend all pending supplemental applications for this NDA, including CBE
`supplements for which FDA has not yet issued an action letter, with the content of labeling
`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this
`supplemental application, as well as annual reportable changes and annotate each change. To
`facilitate review of your submission, provide a highlighted or marked-up copy that shows all
`changes, as well as a clean Microsoft Word version. The marked-up copy should provide
`appropriate annotations, including supplement number(s) and annual report date(s).
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`Reference ID: 3301325
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` NDA 022387/S-008
`Page 3
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` REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`If you have any questions, please call:
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`Lori Anne Wachter, RN, BSN
`Regulatory Project Manager for Safety
`(301) 796-3975
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`Sincerely,
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`{See appended electronic signature page}
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`Mary Ross Southworth, PharmD.
`Deputy Director for Safety
`Division of Cardiovascular and Renal Products
`Office of Drug Evaluation 1
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3301325
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`MARY R SOUTHWORTH
`04/30/2013
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`Reference ID: 3301325
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